This invention relates to novel crystalline forms of an anthracycline antibiotic, particularly daunomycin (also known as daunorubicin), and a process for producing the same.
Daunomycin (also known as daunorubicin; hereinafter abbreviated as DM), which is an anthracycline antibiotic represented by the following formula (I) 
is known to be obtained from a culture medium of an actinomycete, and has a wide anticancer spectrum against experimental animal tumors. As a matter of fact, DM is being widely used as a chemo-therapeutic agent for cancer in clinical applications.
However, the currently available bulk form of DM (DM hydrochloride) is an amorphous powder or a solid which is tentatively classified as crystalline but has high hygroscopicity and poor stability. From the viewpoint of the preparation of DM into medicines, the physical and chemical properties of not only its final bulk powder but also its intermediate products have a great significance. For example, poor chemical stability requires great caution in storage, and high hygroscopicity makes its handling difficult. Moreover, with consideration for its use as a drug, any residual solvent may constitute a fatal shortcoming.
Accordingly, an object of the present invention is to provide a solid product of DM hydrochloride having excellent chemical stability and, preferably, further having low hygroscopicity and an allowable residual solvent content.
The present inventors made repeated investigations with a view to solving the above-described problems and have now found that the crystallization of DM hydrochloride by using a certain solvent system yields a specific crystalline form of DM hydrochloride having excellent chemical stability and, in some instances, this crystalline form also has low hygroscopicity and can solve the problem with residual solvent.
Thus, according to the present invention, there is provided a crystalline form of DM hydrochloride having at least characteristic 2xcex8 values (in degrees) of 6.18, 7.88, 9.82, 11.60, 13.30, 15.80, 20.88 and 23.12 as measured by the X-ray powder diffraction method.
According to the present invention, there is also provided a process for producing the aforesaid crystalline form of DM hydro-chloride from a solution containing DM hydrochloride, the process comprising the steps of preparing the aforesaid solution by using a solvent system composed of a poor solvent for the antibiotic and a good solvent which is miscible with the poor solvent and capable of dissolving the antibiotic; and subjecting the solution so prepared to a crystallization treatment.